Cardiac arrhythmias and ischemic heart disease afflict an estimated 20 million Americans, and possibly ten times as many people worldwide. If left undetected and untreated, they often result in heart attacks and deaths.
An arrhythmia is an irregular heartbeat. The heart beats on its own due to its natural pacemaker, a small cluster of specialized cells called the sinoatrial node (S-A node). The S-A node is located in the right atrium and produces electrical signals at regular intervals that are sent through a pathway in the heart muscle. The S-A node signals follow a natural electrical pathway that helps the heart beat efficiently. An electrical impulse travels from the S-A node through the atrioventricular node (A-V node), a second cluster of cells located near the center of the heart. The A-V node then sends the signals out to the walls of the ventricles.
Normally, the two ventricles contract a fraction of a second after they have been filled with blood from an atrial contraction. This timing sequence is called atrio-ventricular synchrony. Sometimes, however, something goes wrong with the heart's electrical system, and the heartbeat becomes arrhythmic. An arrhythmia can occur when: (1) the S-A node develops an abnormal rate or rhythm; (2) the normal electrical pathway is interrupted, or (3) another part of the heart tries to take over as the pacemaker. Though there are several types of arrhythmias, they all have the commonality of preventing the heart from pumping blood efficiently.
Fast, abnormal heart rhythms, usually over 100 beats per minute, are called tachyarrhythmias. When the heart's electrical signals come from the ventricle instead of the S-A node, this causes an arrhythmia known as ventricular tachycardia (VT). As the heart beats faster, it pumps less blood because there is not enough time for the heart to fill with blood between beats. If this fast heartbeat continues, the brain and body may not receive enough blood and oxygen, causing fainting spells, blackouts, temporary blind spots or dizziness. Eventually, the patient may become unconscious and in extreme cases the heart may stop (cardiac arrest). The most common cause of arrhythmias is heart disease, particularly coronary artery disease, abnormal heart valve function, and heart failure.
VT is a frequent precursor to another type of arrhythmia, ventricular fibrillation (VF). In VF, the heart beats much faster than normal, sometimes over 300 beats a minute. The ventricles “quiver” during VF and do not carry out coordinated contractions. Because little blood is pumped from the heart, VF is a form of cardiac arrest and is fatal unless treated immediately.
Arrhythmias complicate all forms of cardiac disease. Ventricular tachycardia and fibrillation occur commonly in the setting of ischemic heart disease and congestive heart failure (CHF). In the setting of myocardial infarction, ventricular arrhythmias may develop secondarily to ischemia or reperfusion. Reperfusion occurs subsequent to therapies that reestablish flow in an artery that is obstructed by a blood clot, i.e. thrombolytic agents or following an intervention, such as angioplasty, coronary bypass grafting or placement of an intracoronary stent.
A major problem in congestive heart failure is stress hyperglycemia and insulin resistance. As a result of the combination of high circulating levels of free fatty acids and reduced glucose uptake, there is a shift toward fatty acid oxidation, depletion of Krebs cycle intermediates and diminished glucose oxidation. These changes ultimately lead to reduced levels of CrP and loss of energy reserve.
Although the mechanisms underlying ventricular arrhythmias are complex and not fully understood, it has been established that glycolysis plays an important role as the source of ATP to maintain the electrochemical gradient across the cardiac cellular membrane. Potassium (K+), calcium (Ca2+), and sodium (Na+) gradients are all modulated by ATP that arises from glycolysis. Moreover, inhibition of glycolysis is arrhythmogenic, while glucose-insulin-potassium (GIK) infusions in the setting of ischemia are anti-arrhythmic.
Conventional treatment for arrhythmias is aimed at decreasing pacemaker activity and modifying impaired conduction. These treatments usually involve the use of sodium channel blockers, calcium channel blockers and/or beta blockers in an effort to decrease the automaticity, conduction, and excitability of the heart or increase the refractory period of cardiac muscle. While drug treatments are often effective against arrhythmias, drugs frequently have side effects and require the patient to remember to take them on a daily basis. Mild to moderate side effects associated with these drugs include drowsiness, dizziness, nausea, bradycardia, and low blood pressure, while more severe side effects include torsades des pointes (a form of VT) and even sudden death. Further, these drugs can actually cause arrhythmias at increased dosages due to their toxic effects on cardiac conduction at these levels.
Artificial pacemakers are also frequently used in the treatment of arrhythmias. Pacemakers are electronic devices that act in place of the heart's own pacemaker and are programmed to imitate the normal conduction sequence of the heart. Usually they are implanted surgically beneath the skin of the chest and have wires running to the heart. There are several disadvantages associated with the use of pacemakers, including the need to replace the units every 8-10 years and their potential to be interfered with by certain types of equipment, such as magnetic resonance imaging machines (MRIs).
Therapy for arrhythmias can also include devices that deliver a shock to the heart to stop an abnormal rhythm and restore a normal one. Using an electric shock for this purpose is called cardioversion, electroversion, or defibrillation. Usually in this procedure, a large machine that delivers a shock (a defibrillator) is used by a team of doctors and nurses to stop a life-threatening arrhythmia. More recently, a defibrillator about the size of a pack of cards can be implanted surgically in the patient. These small devices, which automatically sense life-threatening arrhythmias and deliver a shock, are used in people who would otherwise die when their heart suddenly stops. Because these defibrillators do not prevent arrhythmias, the patient usually must also take drugs as well.
There is, therefore, a need in the art for a safe and effective composition for preventing and treating cardiac arrhythmias. It is a primary objective of this the present invention to fulfill this need.